Project Summary/Abstract: Abnormalities in the female reproductive tract formation affects 0.1%-3.0% of live births in humans, a main cause of infertility issues when individuals reach their adulthood. It is therefore important to elucidate how the embryo forms a functional female reproductive tract system at the cellular and molecular levels. In the long run, understanding cellular and molecular mechanisms directing the female reproductive tract formation will help us develop better strategies for diagnosis, treatement and prevention of gynecological syndromes and disorders of sexual development. At the early fetal stage, a female embryo possesses both primitive male and female reproductive tracts. The appropriate formation of the female reproductive tract system requires two steps: 1st. regression of the primitive male tract during sexual differentiation; 2nd. retention and differentiation of the primitive female tract into the oviduct, the uterus and the partial vagina. The primitive male and female tracts are surrounded by their respective mesenchyme, which determine the fate and differentiation of the tracts. The focus of this proposal is the male tract mesenchyme, which has been suggested by my published and preliminary results to play critical roles in female reproductive tract formation. During the mentored phase, I will obtain training in next generation sequencing based approaches, and will test my hypothesis that the male tract mesenchyme acts through a transcriptional factor COUP-TFII to regulate the male tract elimination, the 1st step of female reproductive tract formation. In the independent phase, I will use next generation sequencing based approaches to investigate the differentiation of the male tract mesenchyme during the 2nd step of female reproductive tract formation. I will further test my hypothesis that the male tract mesenchyme provides a critical source of mesenchymal cells in the female reproductive tract. At the conclusion of these studies, I expect to establish a model elucidating unexpected roles of the male tract mesenchyme in the formation of the female reproductive tract. My studies will provide us an entry point to understand reproductive tract diseases associated with perturbed mesenchymal differentiation.